131-I-TM-601 Study in Adults With Solid Tumors

NCT ID: NCT00379132

Last Updated: 2009-03-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-08-31
• Study Completion Date: 2008-08-31

Brief Summary

This study is designed to evaluate the ability of intravenously (IV)administered 131-I-labeled TM-601 (chlorotoxin) to provide tumor-specific localization(via radiographic imaging) in patients with recurrent or refractory primary solid tumors with evidence of metastatic involvement. (Refractory tumors are non-responsive to standard treatment.) The safety and tolerability of IV administered 131-I-TM-601 in this patient population will be evaluated as part of this study.

Detailed Description

This is a multi-center, open label, non-randomized, sequential, within-patient dose-escalation study in patients with recurrent or refractory primary solid tumors with metastatic involvement (including brain metastases). Patients will be administered 1 to 3 (Test Doses A, B and Dose C) escalating doses of 131-I-TM-601 by intravenous (IV) administration, with dosimetry (imaging-based evaluation of the dose reaching the target sites) conducted prior to and following administration of each dose. Whole body dosimetry on critical structures including, but not limited to, bone marrow, bladder, brain, liver, and thyroid will be determined. The preliminary results from Test Dose Levels (A and/or B) for each patient will be analyzed prior to treating patients with Dose C.

Patients will be followed until 28 days following the final dose, with a complete clinical assessment and imaging evaluations at the final follow-up visit.

Conditions

Breast Cancer; Non-Small Cell Lung Cancer; Melanoma; Colorectal Cancer; Pancreatic Cancer; Prostate Adenocarcinoma; Glioma; Primary Solid Tumors

Keywords

Glioma; prostatic; breast; non-small cell lung; melanoma; colorectal; pancreatic

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

131-I-TM-601 (chlorotoxin)

Patients will be administered 1 - 3 (Test Doses A, B, and Dose C) escalating doses of 131I-TM601 by intravenous (IV) administration. Each dose will be administered as a single administration, scheduled at one-week intervals.

Test Dose A - 10 mCi (+/- 20%)/0.2 mg TM601 (131I-TM601) Test Dose B - 20 mCi (+/- 20%)/0.4 mg TM601 (131I-TM601) Dose C - 30 mCi (+/- 10%)/0.6 mg TM601 (131I-TM601)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed recurrent or refractory primary solid tumor malignancy. Primary tumor cell type is one of the following: breast, non-small cell lung, melanoma, colorectal, prostatic adenocarcinoma (hormone refractory) or glioma. Note: Patients with a primary solid tumor cell type not listed above, meeting all other selection criteria may be considered eligible, on a case by case basis
• Demonstration of distant metastatic involvement as seen with standard clinical non-invasive imaging techniques (CT/MRI) or on biopsy. Note: on a case-by-case basis, patients with a locally recurrent, unresectable (inoperable) tumor may be considered for inclusion
• Refractory to standard curative treatment
• At least 18 years of age
• Baseline Karnofsky Performance Status (KPS) of 60-100%
• Life expectancy, based on investigator judgement, of greater than 3 months
• Adequate organ and marrow function (as defined in protocol)
• Women of child-bearing potential must have a negative pregnancy test, refrain from nursing, and must agree to use appropriate contraception for the duration of the trial

Exclusion Criteria

• Prior cytotoxic chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
• Patients who have not sufficiently recovered from adverse events due to previously administered agents
• Concurrent treatment with investigational or commercial agents or therapies administered with the intent to treat the patient's malignancy, including chemotherapy, immunotherapy, biological response modifiers, or palliative radiotherapy. Possible exceptions (at the discretion of the investigator) are for hormonal therapy for breast and prostate cancer, hematologic, analgesic, biphosphonate, and any other form of supportive therapy.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to 131-I-labeled chlorotoxin (e.g. iodine or iodine-containing drugs)
• Patients with uncontrolled intercurrent illness.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

TransMolecular

INDUSTRY

Sponsor Role: lead

Responsible Party

TransMolecular, Inc.

Principal Investigators

John Fiveash, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Jeffrey Raizer, M.D.

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Neil Senzer, MD

Role: PRINCIPAL_INVESTIGATOR

Mary Crowley Medical Research Center

Thomas Gribbins, MD

Role: PRINCIPAL_INVESTIGATOR

Lacks Cancer Center at St. Mary's Health Care

Jay-Jiguang Zhu, MD

Role: PRINCIPAL_INVESTIGATOR

Tufts Medical Center

Steven Chmura, MD

Role: PRINCIPAL_INVESTIGATOR

University of Chicago

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Northwestern University, The Robert H. Lurie Comprehensive Cancer Center

Chicago, Illinois, United States

University of Chicago

Chicago, Illinois, United States

Tufts - New England Medical Center

Boston, Massachusetts, United States

Lacks Cancer Center at St. Mary's Health Care

Grand Rapids, Michigan, United States

Mary Crowley Medical Research Center

Dallas, Texas, United States

Countries

United States

References

Mamelak AN, Jacoby DB. Targeted delivery of antitumoral therapy to glioma and other malignancies with synthetic chlorotoxin (TM-601). Expert Opin Drug Deliv. 2007 Mar;4(2):175-86. doi: 10.1517/17425247.4.2.175.

Reference Type: BACKGROUND

PMID: 17335414 (View on PubMed)

Mamelak AN, Rosenfeld S, Bucholz R, Raubitschek A, Nabors LB, Fiveash JB, Shen S, Khazaeli MB, Colcher D, Liu A, Osman M, Guthrie B, Schade-Bijur S, Hablitz DM, Alvarez VL, Gonda MA. Phase I single-dose study of intracavitary-administered iodine-131-TM-601 in adults with recurrent high-grade glioma. J Clin Oncol. 2006 Aug 1;24(22):3644-50. doi: 10.1200/JCO.2005.05.4569.

Reference Type: BACKGROUND

PMID: 16877732 (View on PubMed)

Hockaday DC, Shen S, Fiveash J, Raubitschek A, Colcher D, Liu A, Alvarez V, Mamelak AN. Imaging glioma extent with 131I-TM-601. J Nucl Med. 2005 Apr;46(4):580-6.

Reference Type: BACKGROUND

PMID: 15809479 (View on PubMed)

Lyons SA, O'Neal J, Sontheimer H. Chlorotoxin, a scorpion-derived peptide, specifically binds to gliomas and tumors of neuroectodermal origin. Glia. 2002 Aug;39(2):162-73. doi: 10.1002/glia.10083.

Reference Type: BACKGROUND

PMID: 12112367 (View on PubMed)

Other Identifiers

TM601-003

Identifier Type: -

Identifier Source: org_study_id